Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling (WP3675)
Mus musculus
The signaling pathway that involves insulin-like growth factor 1 (IGF1), and a variety of other components that affect the pathway, plays an important role in the regulation of skeletal muscle growth. The kinase Akt, or protein kinase B (PKB), is a central component in the pathway and is involved in both muscle synthesis, through mammalian target of rapmycin (mTOR) and glycogen synthase kinase 3B (GSK3B), and muscle degradation, through the transcription factors of the FoxO family. The pathway also involves several feedback loops such as the negative feedback of S6K, phosphorylated by mTORC1, which inhibits IRS, or the positive feedback of mTORC2, which is necessary to maximize the activation of Akt. A variety of other factors and pathways also influence the IGF1-Akt signaling pathway at various points. This pathway is based on figure 3 from Schiaffino et al.
Authors
AAR&Co , Alex Pico , Egon Willighagen , Martina Summer-Kutmon , and Kristina HanspersActivity
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Organisms
Mus musculusCommunities
Annotations
Pathway Ontology
growth factor signaling pathway insulin-like growth factor signaling pathway signaling pathwayCell Type Ontology
cell of skeletal muscle| Label | Type | Compact URI | Comment |
|---|---|---|---|
| SMAD3 | GeneProduct | ensembl:ENSMUSG00000032402 | |
| PGC1 | GeneProduct | ensembl:ENSMUSG00000029167 | |
| FoxO | GeneProduct | uniprot:Q9R1E0 | family of transcription factors |
| SMAD2 | GeneProduct | ensembl:ENSMUSG00000024563 | |
| AMPK | GeneProduct | ensembl:ENSMUSG00000029513 | |
| Myostatin | GeneProduct | ensembl:ENSMUSG00000026100 | |
| TWEAK | GeneProduct | ensembl:ENSMUSG00000035678 | |
| AKT1 | GeneProduct | ensembl:ENSMUSG00000001729 | |
| Integrin B1 | GeneProduct | ensembl:ENSMUSG00000025809 | |
| TNFrec | GeneProduct | ensembl:ENSMUSG00000030341 | |
| MURF1 | GeneProduct | ensembl:ENSMUSG00000028834 | TRIM63 |
| IRS1 | GeneProduct | ensembl:ENSMUSG00000055980 | not sure, because also 2, 3, 4 |
| PLD1 | GeneProduct | ensembl:ENSMUSG00000027695 | |
| ILK | GeneProduct | ensembl:ENSMUSG00000030890 | |
| PDK1 | GeneProduct | ensembl:ENSMUSG00000006494 | |
| MTOR | GeneProduct | ensembl:ENSMUSG00000028991 | effect of AKT on MTOR is indirectPart of two multiprotein complexes, TORC 1 and TORC 2 |
| S6K | GeneProduct | ensembl:ENSMUSG00000020516 | |
| TNFa | GeneProduct | ensembl:ENSMUSG00000024401 | |
| PTEN | GeneProduct | ensembl:ENSMUSG00000013663 | |
| IGF1rec | GeneProduct | ensembl:ENSMUSG00000005533 | |
| IGF1 | GeneProduct | ensembl:ENSMUSG00000020053 | |
| Igfbp5 | GeneProduct | ensembl:ENSMUSG00000026185 | most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor |
| ActRIIB | GeneProduct | ensembl:ENSMUSG00000061393 | |
| mTORC2 | GeneProduct | uniprot:Q9JLN9 | complex of mTOR when bound to rictorrapamycin insensitivemaximizes activation of AKT1 |
| NFKB1 | GeneProduct | ensembl:ENSMUSG00000028163 | |
| Igfbp1 | GeneProduct | ensembl:ENSMUSG00000020429 | most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor |
| Igfbp3 | GeneProduct | ensembl:ENSMUSG00000020427 | most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor |
| Igfbp4 | GeneProduct | ensembl:ENSMUSG00000017493 | most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor |
| Igfbp2 | GeneProduct | ensembl:ENSMUSG00000039323 | most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor |
| Igfbp7 | GeneProduct | ensembl:ENSMUSG00000036256 | most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor |
| Igfbp6 | GeneProduct | ensembl:ENSMUSG00000023046 | most important of grup of IGF binding proteins that inhibit binding of IGF1 to its receptor |
| JNK | Protein | uniprot:Q8BI36 |
References
- Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Schiaffino S, Mammucari C. Skelet Muscle. 2011 Jan 24;1(1):4. PubMed Europe PMC Scholia